Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles

• Published in: Toxicology and applied pharmacology Vol. 266; no. 3; pp. 356 - 365
• Main Authors: Rezvanfar, Mohammad Amin, Rezvanfar, Mohammad Ali, Shahverdi, Ahmad Reza, Ahmadi, Abbas, Baeeri, Maryam, Mohammadirad, Azadeh, Abdollahi, Mohammad
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.02.2013; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; ALKYLATING AGENTS; Animals; ANTIOXIDANTS; Biological and medical sciences; BIOLOGICAL MARKERS; BIOLOGICAL STRESS; biomarkers; BLOOD; CATALASE; Catalase - blood; CATS; CHROMATIN; Chromatin - drug effects; Chromatin - metabolism; Cisplatin; Cisplatin - toxicity; CONCENTRATION RATIO; DNA ADDUCTS; DNA Damage; DNA DAMAGES; Drug toxicity and drugs side effects treatment; ECOLOGICAL CONCENTRATION; Enzymes; Free radicals; GLUTATHIONE; Glutathione peroxidase; Glutathione Peroxidase - blood; Lipid peroxidation; Male; Medical sciences; Metal Nanoparticles - administration & dosage; OXIDATION; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Peroxynitrite; Peroxynitrous Acid - blood; Pharmacology. Drug treatments; Random Allocation; RATS; Rats, Wistar; Reproductive toxicity; SELENIUM; Selenium - pharmacology; Selenium nano-particles; Sperm; Sperm Count; Sperm DNA damage; Sperm Motility - drug effects; Sperm Motility - physiology; SPERMATOGENESIS; Spermatogenesis - drug effects; SPERMATOZOA; SUPEROXIDE DISMUTASE; Superoxide Dismutase - blood; TESTES; Testis - drug effects; Testis - enzymology; Testis - metabolism; TESTOSTERONE; Testosterone - blood; Thiobarbituric Acid Reactive Substances - metabolism; Toxicants; TOXICITY; Toxicity: urogenital system; Oxidative stress; Selenium nano-particles; Reproductive toxicity; Cisplatin; Sperm DNA damage; Antineoplastic agent; Chromatin; Spermatozoa; Rat; Toxicity; Germinal cell; Particle; Prevention; Selenium; Mechanism of action; Platinum II Complexes; Reproduction diseases; Semen; Rodentia; Micronutrient; Alkylating agent; Vertebrata; Mammalia; Animal; DNA; Lesion
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2012.11.025

Cisplatin (CIS), an anticancer alkylating agent, induces DNA adducts and effectively cross links the DNA strands and so affects spermatozoa as a male reproductive toxicant. The present study investigated the cellular/biochemical mechanisms underlying possible protective effect of selenium nano-particles (Nano-Se) as an established strong antioxidant with more bioavailability and less toxicity, on reproductive toxicity of CIS by assessment of sperm characteristics, sperm DNA integrity, chromatin quality and spermatogenic disorders. To determine the role of oxidative stress (OS) in the pathogenesis of CIS gonadotoxicity, the level of lipid peroxidation (LPO), antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and peroxynitrite (ONOO) as a marker of nitrosative stress (NS) and testosterone (T) concentration as a biomarker of testicular function were measured in the blood and testes. Thirty-two male Wistar rats were equally divided into four groups. A single IP dose of CIS (7mg/kg) and protective dose of Nano-Se (2mg/kg/day) were administered alone or in combination. The CIS-exposed rats showed a significant increase in testicular and serum LPO and ONOO level, along with a significant decrease in enzymatic antioxidants levels, diminished serum T concentration and abnormal histologic findings with impaired sperm quality associated with increased DNA damage and decreased chromatin quality. Coadministration of Nano-Se significantly improved the serum T, sperm quality, and spermatogenesis and reduced CIS-induced free radical toxic stress and spermatic DNA damage. In conclusion, the current study demonstrated that Nano-Se may be useful to prevent CIS-induced gonadotoxicity through its antioxidant potential. [Display omitted] ► Cisplatin (CIS) affects spermatozoa as a male reproductive toxicant. ► Effect of Nano-Se on CIS-induced spermatotoxicity was investigated. ► CIS-exposure induces oxidative sperm DNA damage and impairs steroidogenesis. ► Nano-Se retained sperm quality against CIS-induced free radicals toxic stress.